Date Published: January 31, 2019
Publisher: Public Library of Science
Author(s): Jun Ma, Yujia Zhai, Ming Chen, Kai Zhang, Quan Chen, Xiaoyun Pang, Fei Sun, Shannon Wing-Ngor Au.
Mitochondrial fission is facilitated by dynamin-related protein Drp1 and a variety of its receptors. However, the molecular mechanism of how Drp1 is recruited to the mitochondrial surface by receptors MiD49 and MiD51 remains elusive. Here, we showed that the interaction between Drp1 and MiD51 is regulated by GTP binding and depends on the polymerization of Drp1. We identified two regions on MiD51 that directly bind to Drp1, and found that dimerization of MiD51, relevant to residue C452, is required for mitochondrial dynamics regulation. Our Results have suggested a multi-faceted regulatory mechanism for the interaction between Drp1 and MiD51 that illustrates the potentially complicated and tight regulation of mitochondrial fission.
Mitochondria are highly dynamic organelles that constantly undergo fusion, fission and move along the cytoskeleton . Beyond the primary function of mitochondrial dynamics in controlling organelle shape, size, number and distribution, it is clear that dynamics are also crucial to specific physiological functions, such as cell cycle progression, quality control and apoptosis [2–5]. Dysfunction in mitochondrial dynamics has been implicated a variety of human diseases, including neurodegenerative diseases, the metabolism disorder diabetes and cardiovascular diseases [6,7].
The role of MiD51 in mitochondrial fission has been well established [15,17,26–29]. MiD51 mediates mitochondrial fission by recruiting Drp1 to the outer mitochondrial membrane and regulating its assembly and mitochondrial fission activity in a GTP-dependent manner. We have elucidated in molecular detail how the interaction between MiD51 and Drp1 is regulated by multi-faceted mechanism.